Novel molecular mechanisms

Calcium cycling proteins influence myocardial repolarization

A surprising finding from our GWAS of electrocardiographic QT interval, a marker of sudden cardiac death risk, was the dramatic over-representation of genes involved in calcium cycling in heart muscle cells. The system that regulates heart muscle contraction appears to directly influence myocardial repolarization, the electrical resetting of the heart muscle cell after each beat. This points to disordered calcium signaling as a mechanism that contributes to the ventricular arrhythmias in heart failure. This work has led to an R01 grant in which we are testing the impact of genetic variants on exposure to psychiatric medications that prolong the QT interval in order to identify individuals at high risk of potentially fatal side effects. [Arking Nature Genetics 2014]